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1.
Deferasirox reduces oxidative DNA damage in bone marrow cells from myelodysplastic patients and improves their differentiation capacity.
Jiménez-Solas, T, López-Cadenas, F, Aires-Mejía, I, Caballero-Berrocal, JC, Ortega, R, Redondo, AM, Sánchez-Guijo, F, Muntión, S, García-Martín, L, Albarrán, B, et al
British journal of haematology. 2019;(1):93-104
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Abstract
Patients with low-risk myelodysplastic syndromes (MDS) usually develop iron overload. This leads to a high level of oxidative stress in the bone marrow (BM) and increases haematopoietic cell dysfunction. Our objective was to analyse whether chelation with deferasirox (DFX) alleviates the consequences of oxidative stress and improves BM cell functionality. We analysed 13 iron-overloaded MDS patients' samples before and 4-10 months after treatment with DFX. Using multiparametric flow cytometry analysis, we measured intracellular reactive oxygen species (ROS), DNA oxidation and double strand breaks. Haematopoietic differentiation capacity was analysed by colony-forming unit (CFU) assays. Compared to healthy donors, MDS showed a higher level of intracellular ROS and DNA oxidative damage in BM cells. DNA oxidative damage decreased following DFX treatment. Furthermore, the clonogenic assays carried out before treatment suggest an impaired haematopoietic differentiation. DFX seems to improve this capacity, as illustrated by a decreased cluster/CFU ratio, which reached values similar to controls. We conclude that BM cells from MDS are subject to higher oxidative stress conditions and show an impaired haematopoietic differentiation. These adverse features seem to be partially rectified after DFX treatment.
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Modulation of plasma antioxidant levels, glutathione S-transferase activity and DNA damage in smokers following a single portion of broccoli: a pilot study.
Riso, P, Del Bo', C, Vendrame, S, Brusamolino, A, Martini, D, Bonacina, G, Porrini, M
Journal of the science of food and agriculture. 2014;(3):522-8
Abstract
BACKGROUND Broccoli is a rich source of bioactive compounds (i.e. glucosinolates, carotenoids, vitamin C and folate) that may exert an antioxidant effect and reduce oxidative damage. The objective of this pilot study was to investigate the effect of broccoli consumption on carotenoids, vitamin C and folate absorption, glutathione S-transferase (GST) activity, and oxidatively induced DNA damage in male smokers. METHODS Ten healthy subjects consumed a single portion of steamed broccoli (250 g) with cooked pasta. Blood was drawn at baseline and at 3, 6 and 24 h from consumption. RESULTS Broccoli significantly (P ≤ 0.01) increased plasma level of vitamin C and folate (+35% and 70%, respectively) at 3 h, and β-carotene (+8%) at 6 h. A modulation of GST activity occurred in plasma 6 h after broccoli consumption. A significant (P ≤ 0.01) reduction of the levels of H₂O₂-induced DNA damage (-18%) was observed in blood mononuclear cells 24 h after broccoli intake in GSTM1 positive, but not in GSTM1 null subjects. CONCLUSION One portion of broccoli increased plasma antioxidant levels, modulated plasma GST activity and improved cell resistance against H₂O₂-induced DNA damage in healthy smokers. These results support the importance of consuming fruit and vegetable regularly.
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Effects of oral antioxidant treatment upon the dynamics of human sperm DNA fragmentation and subpopulations of sperm with highly degraded DNA.
Abad, C, Amengual, MJ, Gosálvez, J, Coward, K, Hannaoui, N, Benet, J, García-Peiró, A, Prats, J
Andrologia. 2013;(3):211-6
Abstract
The primary aim of this study was to determine the effect of oral antioxidant treatment (1500 mg of l-Carnitine; 60 mg of vitamin C; 20 mg of coenzyme Q10; 10 mg of vitamin E; 10 mg of zinc; 200 μg of vitamin B9; 50 μg of selenium; 1 μg of vitamin B12) during a time period of 3 months upon the dynamics of sperm DNA fragmentation following varying periods of sperm storage (0 h, 2 h, 6 h, 8 h and 24 h) at 37 °C in a cohort of 20 infertile patients diagnosed with asthenoteratozoospermia. A secondary objective was to use the sperm chromatin dispersion test (SCD) to study antioxidant effects upon a specific subpopulation of highly DNA degraded sperm (DDS). Semen parameters and pregnancy rate (PR) were also determined. Results showed a significant improvement of DNA integrity at all incubation points (P < 0.01). The proportion of DDS was also significantly reduced (P < 0.05). Semen analysis data showed a significant increase in concentration, motility, vitality and morphology parameters. Our results suggest that antioxidant treatment improves sperm quality not only in terms of key seminal parameters and basal DNA damage, but also helps to maintain DNA integrity. Prior administration of antioxidants could therefore promote better outcomes following assisted reproductive techniques.
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Prolonged coenzyme Q10 treatment in Down syndrome patients: effect on DNA oxidation.
Tiano, L, Padella, L, Santoro, L, Carnevali, P, Principi, F, Brugè, F, Gabrielli, O, Littarru, GP
Neurobiology of aging. 2012;(3):626.e1-8
Abstract
Oxidative stress is known to play a relevant role in Down syndrome (DS) and its effects are documented from embryonic life. Oxidative DNA damage has been shown to be significantly elevated in Down syndrome patients, and this has been indicated as an early event promoting neurodegeneration and Alzheimer type dementia. The aim of this study was to investigate the efficacy of coenzyme Q(10) (CoQ(10)) in delaying the effect of oxidative damage in these patients. In our previous study we demonstrated a mild protective effect of CoQ(10) on DNA, although the treatment was unable to modify the overall extent of oxidative damage at the patient level. Possible limitations of the previous study were: time of treatment (6 months) or spectrum of DNA lesions detected. In order to overcome these limitations we planned a continuation of the trial aimed at evaluating the effects of CoQ(10) following a prolonged treatment. Our results highlight an age-specific reduction in the percentage of cells showing the highest amount of oxidized bases, indicating a potential role of CoQ(10) in modulating DNA repair mechanisms.
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Supplementation of a western diet with golden kiwifruits (Actinidia chinensis var.'Hort 16A':) effects on biomarkers of oxidation damage and antioxidant protection.
Brevik, A, Gaivão, I, Medin, T, Jørgenesen, A, Piasek, A, Elilasson, J, Karlsen, A, Blomhoff, R, Veggan, T, Duttaroy, AK, et al
Nutrition journal. 2011;:54
Abstract
BACKGROUND The health positive effects of diets high in fruits and vegetables are generally not replicated in supplementation trials with isolated antioxidants and vitamins, and as a consequence the emphasis of chronic disease prevention has shifted to whole foods and whole food products. METHODS We carried out a human intervention trial with the golden kiwifruit, Actinidia chinensis, measuring markers of antioxidant status, DNA stability, plasma lipids, and platelet aggregation. Our hypothesis was that supplementation of a normal diet with kiwifruits would have an effect on biomarkers of oxidative status. Healthy volunteers supplemented a normal diet with either one or two golden kiwifruits per day in a cross-over study lasting 2 × 4 weeks. Plasma levels of vitamin C, and carotenoids, and the ferric reducing activity of plasma (FRAP) were measured. Malondialdehyde was assessed as a biomarker of lipid oxidation. Effects on DNA damage in circulating lymphocytes were estimated using the comet assay with enzyme modification to measure specific lesions; another modification allowed estimation of DNA repair. RESULTS Plasma vitamin C increased after supplementation as did resistance towards H₂O₂-induced DNA damage. Purine oxidation in lymphocyte DNA decreased significantly after one kiwifruit per day, pyrimidine oxidation decreased after two fruits per day. Neither DNA base excision nor nucleotide excision repair was influenced by kiwifruit consumption. Malondialdehyde was not affected, but plasma triglycerides decreased. Whole blood platelet aggregation was decreased by kiwifruit supplementation. CONCLUSION Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage.
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Effects of Melissa officinalis L. on oxidative status and DNA damage in subjects exposed to long-term low-dose ionizing radiation.
Zeraatpishe, A, Oryan, S, Bagheri, MH, Pilevarian, AA, Malekirad, AA, Baeeri, M, Abdollahi, M
Toxicology and industrial health. 2011;(3):205-12
Abstract
The aim of this study was to determine the capability of Melissa officinalis L. (Lemon balm) infusion on improvement of oxidative stress status in radiology staff that were exposed to persistent low-dose radiation during work. The study was a before-after clinical trial performed on 55 radiology staff. They were asked to drink Lemon balm infusion which was prepared like a tea bag twice daily (1.5 g/100 mL) for 30 days. In the plasma, lipid peroxidation, DNA damage, catalase, superoxide dismutase, myeloperoxidase, and glutathione peroxidase activity were measured before and after using Lemon balm infusion.Use of Lemon balm infusion in radiology unit workers resulted in a significant improvement in plasma levels of catalase, superoxide dismutase, and glutathione peroxidase and a marked reduction in plasma DNA damage, myeloperoxidase, and lipid peroxidation. It is concluded that infusion of Lemon balm markedly improve oxidative stress condition and DNA damage in radiology staff when used as a dietary supplement for radiation protection.
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Effect of dark chocolate on plasma epicatechin levels, DNA resistance to oxidative stress and total antioxidant activity in healthy subjects.
Spadafranca, A, Martinez Conesa, C, Sirini, S, Testolin, G
The British journal of nutrition. 2010;(7):1008-14
Abstract
Dark chocolate (DC) may be cardioprotective by antioxidant properties of flavonoids. We investigated the effect of DC (860 mg polyphenols, of which 58 mg epicatechin) compared with white chocolate (WC; 5 mg polyphenols, undetectable epicatechin) on plasma epicatechin levels, mononuclear blood cells (MNBC) DNA damage and plasma total antioxidant activity (TAA). Twenty healthy subjects followed a balanced diet (55 % of energy from carbohydrates, 30 % from fat and 1 g protein/kg body weight) for 4 weeks. Since the 14th day until the 27th day, they introduced daily 45 g of either WC (n 10) or DC (n 10). Whole experimental period was standardised in antioxidant intake. Blood samples were collected at T(0), after 2 weeks (T(14)), 2 h and 22 h after the first chocolate intake (T(14+2 h) and T(14+22 h)), and at 27th day, before chocolate intake (T(27)), 2 h and 22 h after (T(27+2 h) and T(27+22 h)). Samples, except for T(14+2 h) and T(27+2 h), were fasting collected. Detectable epicatechin levels were observed exclusively 2 h after DC intake (T(14+2 h) = 0.362 (se 0.052) micromol/l and T(27+2 h) = 0.369 (se 0.041) micromol/l); at the same times corresponded lower MNBC DNA damages (T(14+2 h) = - 19.4 (se 3.4) % v. T(14), P < 0.05; T(27+2 h) = - 24 (se 7.4) % v. T(27), P < 0.05; T(14+2 h) v. T(27+2 h), P = 0.7). Both effects were no longer evident after 22 h. No effect was observed on TAA. WC did not affect any variable. DC may transiently improve DNA resistance to oxidative stress, probably for flavonoid kinetics.
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A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation.
Murray, JC, Burch, JA, Streilein, RD, Iannacchione, MA, Hall, RP, Pinnell, SR
Journal of the American Academy of Dermatology. 2008;(3):418-25
Abstract
BACKGROUND Skin cancer and photoaging changes result from ultraviolet (UV)-induced oxidative stress. Topical antioxidants may protect skin from these effects. OBJECTIVE We sought to determine whether a stable topical formulation of 15% L-ascorbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid (CEFer) could protect human skin in vivo from substantial amounts of solar-simulated UV radiation. METHODS CEFer and its vehicle were applied to separate patches of normal-appearing human skin for 4 days. Each patch was irradiated with solar-simulated UV, 2 to 10 minimal erythema doses, at 2-minimal erythema dose intervals. One day later, skin was evaluated for erythema and sunburn cells, and immunohistochemically for thymine dimers and p53. UV-induced cytokine formation, including interleukin (IL)-1alpha, IL-6, IL-8, and IL-10, and tumor necrosis factor-alpha, were evaluated by real-time polymerase chain reaction. RESULTS CEFer provided significant and meaningful photoprotection for skin by all methods of evaluation. LIMITATIONS The number of patients evaluated was relatively small. CONCLUSION CEFer provided substantial UV photoprotection for skin. It is particularly effective for reducing thymine dimer mutations known to be associated with skin cancer. Its mechanism of action is different from sunscreens and would be expected to supplement the sun protection provided by sunscreens.
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Effects of a high daily dose of soy isoflavones on DNA damage, apoptosis, and estrogenic outcomes in healthy postmenopausal women: a phase I clinical trial.
Pop, EA, Fischer, LM, Coan, AD, Gitzinger, M, Nakamura, J, Zeisel, SH
Menopause (New York, N.Y.). 2008;(4 Pt 1):684-92
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Abstract
OBJECTIVE A phase I double-blind clinical trial was conducted to evaluate the effects of a high oral dose of soy isoflavones administered daily for 84 days to healthy postmenopausal women. Principal outcome measures included DNA damage, apoptosis, and changes indicative of estrogenic stimulation. DESIGN After eligibility and equol-producer status were determined, stratified randomization was used to assign women to the isoflavone (active) or placebo group. Of the 30 women who completed the study, 18 were in the active group. DNA damage was assessed via COMET and apurinic/apyrimidinic site assays in lymphocytes. Apoptosis was evaluated via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and activated caspase-3 assays in lymphocytes. Estrogenic/antiestrogenic effects were assessed using a self-report questionnaire and by assaying for estrogen, follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin in blood. RESULTS In treated postmenopausal women, there was no indication that high doses of soy isoflavones caused DNA strand breakage, increased apurinic/apyrimidinic sites, or increased apoptosis in peripheral lymphocytes. There were no significant changes in mean values for estrogenic effects or other laboratory measurements. Very few adverse events occurred, and the only drug-related adverse events were mild or grade 1 in severity. CONCLUSIONS Unconjugated soy isoflavones appear to be safe and well tolerated in healthy postmenopausal women at doses of 900 mg/day.
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Consumption of Brussels sprouts protects peripheral human lymphocytes against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and oxidative DNA-damage: results of a controlled human intervention trial.
Hoelzl, C, Glatt, H, Meinl, W, Sontag, G, Haidinger, G, Kundi, M, Simic, T, Chakraborty, A, Bichler, J, Ferk, F, et al
Molecular nutrition & food research. 2008;(3):330-41
Abstract
To find out if the cancer protective effects of Brussels sprouts seen in epidemiological studies are due to protection against DNA-damage, an intervention trial was conducted in which the impact of vegetable consumption on DNA-stability was monitored in lymphocytes with the comet assay. After consumption of the sprouts (300 g/p/d, n = 8), a reduction of DNA-migration (97%) induced by the heterocyclic aromatic amine 2-amino-1-methyl-6-phenyl-imidazo-[4,5-b]pyridine (PhIP) was observed whereas no effect was seen with 3-amino-1-methyl-5H-pyrido[4,3-b]-indole (Trp-P-2). This effect protection may be due to inhibition of sulfotransferase 1A1, which plays a key role in the activation of PhIP. In addition, a decrease of the endogenous formation of oxidized bases was observed and DNA-damage caused by hydrogen peroxide was significantly (39%) lower after the intervention. These effects could not be explained by induction of antioxidant enzymes glutathione peroxidase and superoxide dismutase, but in vitro experiments indicate that sprouts contain compounds, which act as direct scavengers of reactive oxygen species. Serum vitamin C levels were increased by 37% after sprout consumption but no correlations were seen between prevention of DNA-damage and individual alterations of the vitamin levels. Our study shows for the first time that sprout consumption leads to inhibition of sulfotransferases in humans and to protection against PhIP and oxidative DNA-damage.